Pandinus imperator scorpion venom blocks voltage-gated K+ channels in human lymphocytes.
Using the patch-clamp technique, we determined that Pandinus imperator scorpion venom blocked whole-cell n-type K+ currents in human peripheral blood lymphocytes in a dose-dependent manner with Kd = 0.02 microgram/ml. K+ channel block was instantaneous and removable by washing with venom-free extracellular solution. The venom-induced block was independent of membrane potential. The venom did not influence activation and inactivation kinetics of the K+ channels, however, accelerated recovery from inactivation. Purified peptides Pi1, Pi2, and Pi3 from the P. imperator venom powerfully blocked Kv1.3 channels in human lymphocytes with Kd values of 9.7 nM, 50 pM, and 0.5 nM, respectively. Flow cytometric membrane potential measurements with the oxonol dye showed that Pi2, the most effective peptide toxin of the P. imperator venom, depolarizes human lymphocytes in accordance with its K+ channel blocking effect.
Péter
M
M
Department of Biophysics and Cell Biology, University Medical School, Debrecen, Hungary.
Varga
Z
Z
Panyi
G
G
Bene
L
L
Damjanovich
S
S
Pieri
C
C
Possani
L D
LD
Gáspár
R
R
D001463:Barbiturates / Q000378:metabolism; D004594:Electrophysiology; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D007555:Isoxazoles / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011485:Protein Binding; D012604:Scorpion Venoms / Q000494:pharmacology*; D014118:Toxins, Biological / Q000302:isolation & purification / Q000494:pharmacology*
D001463:Barbiturates; D005456:Fluorescent Dyes; D007555:Isoxazoles; C101360:Pi2 toxin; C101361:Pi3 toxin, scorpion; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D014118:Toxins, Biological; C052795:bis(1,3-dibutylbarbiturate)trimethine oxonol